We originally proposed that a significant contributor to the hematotoxicity of benzene is a metabolite(s) produced through the opening of the benzene ring and having an alpha beta-unsaturated aldehyde as part of its structure. Our findings include the demon- stration that trans, trans-muconaldehyde (TTM) is formed from benzene during incubation with mouse liver microsomes, and that this compound has short term hematological toxicity similar to that of benzene at a dose range consistent with extrapolating a potential major role in benzene hematotoxicity. We propose further studies which have two major objectives, the confirmation and exploitation of these findings in relation to benzene hematotoxicity, and the extension of the overall concept to other aromatic compounds. The specific aims of the protocol are: 1. To further assess the hematologic toxicity of TTM in vitro in laboratory animals. 2. To explore whether the known difference in susceptibility to benzene among laboratory animal strains could be due to differences in the extent of formation of TTM, or hematological response to TTM. 3. To ascertain whether TTM is formed in the bone marrow. 4. To assess the formation of macromolecular adducts of TTM in vivo with the aim of both providing an assay of TTM formation and of providing information about the toxicology of TTM. 5. To ascertain the extent to which muconic acid formation is a marker of the production of muconaldehyde in vivo. 6. To compare the in vivo toxicity of TTM with other benzene metabolites.